APC and neoplasm: Here, the authors amassed a unique collection of genetically engineered mouse models (GEMMs) harboring conditional alleles that mimic acquired somatic alterations observed in human sporadic CRC, including loss of the tumor suppressors APC and TP53 and gain of oncogenic BRAF and KRAS. To gain an understanding of the utility of these models, gene signatures were derived and used to stratify genomically heterogeneous clinically annotated patient samples, as well as human cell lines treated with targeted inhibitors.